Lung cancer is one of the more common malignancy effecting the population. Once a tumor is diagnosed, the overall prognosis is poor, with an overall five year survival rate of only 13%. However, early detection and treatment of lung cancer can significantly improve 5 year survival rates. In those cases where the disease is detected early and surgical resection is feasible, the five year survival rate increases to 40%. For those at high risk for development of lung cancer intensive monitoring has not been effective in reducing the incidence of the disease or its outcome due in part to the inability to define early stages of the disease when transformation is first occurring within normal cell populations of the tracheobronchial tree.
Monoclonal antibodies to tumor-associated antigens provide useful reagents for diagnosis of cancer and for targeting of various anti-tumor agents such as radioisotopes, chemotherapeutic drugs and toxins to the site of the tumor. Many monoclonal antibodies reactive against carcinoma-associated antigens are known. These known antibodies bind to a variety of different carcinoma-associated antigens that include glycoproteins but for the most part bind to the carbohydrate moiety. For example, monoclonal antibodies that bind to glycoprotein antigens on specific types of carcinomas include those described in U.S. Pat. Nos. 4,737,579; 4,753,894; 4,579,827 and 4,713,352.
Since many tumor cells shed their membrane glycoproteins into surrounding body fluids such as serum, or bronchial secretions in the case of squamous cell carcinomas, the possibility of detecting shed antigen using monoclonal antibodies in an ELISA is a possible approach to early detection. This is the approach taken for detection of tumor markers such as PSA and CEA in serum. As an example, supernatants of the bronchial lavage could be used in immunoassays designed for early detection of transformed cells in bronchial epithelium where shed antigen appears in the supernatant fluid. To date, assays designed to define tumor cells in sputum samples have proven to be ineffective because of the unavailability of monoclonal antibodies capable of differentiating between normal and abnormal squamous cells or to be able to define genotypically altered cells before the phenotypic changes of malignancy are evident.
Most studies have employed epithelial markers such as cytokeratin antibodies which are non-specific and will react with most if not all epithelial cells. Thus, better monoclonal antibody based diagnostic and prognostic markers and more sensitive tests for use in defining clinical lung cancer are needed. Ideally the monoclonal antibodies will detect the expression of a specific tumor antigen at an early time when clinical disease is not obvious. Such a tumor antigen defined by a monoclonal antibody could be used as a target for immunotherapy directed against the specific tumor antigen expressed on the surface of the cell. Such antibodies may also be of prognostic value based their ability to identify markers expressed at different stages of disease or that function differently, i.e., e-capherin, growth factor or receptor.